Evolving Concepts in Helicobacter pylori Management.

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

A HIGH-RESOLUTION MICROENDOSCOPE IMPROVES ESOPHAGEAL CANCER SCREENING AND SURVEILLANCE: IMPLICATIONS FOR UNDERSERVED GLOBAL SETTINGS BASED ON AN INTERNATIONAL, RANDOMIZED CONTROLLED TRIAL.

BACKGROUND AND AIMS: Lugol's chromoendoscopy (LCE)-based detection of esophageal squamous cell neoplasia (ESCN) is limited by low specificity. High-resolution microendoscopy (HRME) was shown to improve specificity and reduce unnecessary biopsies when used by academic endoscopists. In this international, randomized controlled trial, we determined the clinical impact, efficiency, and performance of HRME in true global health contexts with a range of providers. METHODS: Subjects undergoing screening or surveillance for ESCN by expert and novice endoscopists were enrolled in China and the U.S. from diverse clinical settings. Subjects were randomized to LCE (standard-of-care) or LCE+HRME (experimental). Primary outcomes were efficiency and clinical impact of LCE vs. LCE+HRME, using gold-standard, consensus pathology. RESULTS: Among 916 consented subjects, 859 (93.8%) were recruited in China and 36 (3.9%) in the U.S.; 21 (2.3%) were excluded due to incomplete procedure or data. In the screening arm, 217 subjects were randomized to LCE, 204 to LCE+HRME; in the surveillance arm, 236 were randomized to LCE, 238 to LCE+HRME. HRME increased efficiency in screening: diagnostic yield (neoplastic/total biopsies) improved from 20.0% (95% confidence interval [CI] 12.7-29.2%) to 51.7% (95% CI 32.5-70.6%) with 65.2% (95% CI 54.6-74.9%) of biopsies potentially saved and 59.7% (95% CI 47.5-71.1%) of subjects potentially spared any biopsy. Six subjects (0.7%) had neoplasia missed by the endoscopist on HRME (false negatives); of these, 3 were moderate or high-grade dysplasia missed by novices. CONCLUSION: A low-cost microendoscope improves the efficiency and clinical impact of ESCN screening and surveillance when combined with LCE. HRME may spare unnecessary biopsies leading to cost savings in underserved global settings where the disease is prevalent. CLINICALTRIALS: gov, Number NCT02029937.

Patient- and system-level factors associated with racial/ethnic disparities in the delivery of guideline-concordant therapy among US patients with gastric cancer.

BACKGROUND: Disparities in gastric cancer (GC) outcomes show a higher disease burden among minorities. We aimed to evaluate the associations between sociodemographic and system-level factors and guideline-concordant treatment among GC patients. METHODS: Cohort study with GC patients in the National Cancer Data Base (2006-2018) treated with upfront resection or neoadjuvant therapy (NAT). We used logistic regression to identify associations between deviations from guideline-concordant therapy and patient- and system-level factors, and Cox regression models to assess risk of death. RESULTS: The cohort included 43 597 GC patients treated with endoscopic resection (8.9%), surgery only (47.1%), surgery and adjuvant therapy (20.6%), or NAT followed by surgery (23.5%). A total of 31 470 patients (72.2%) received guideline-concordant therapy. Relative to Non-Hispanic Whites (NHWs), Non-Hispanic Blacks (NHBs) (odds ratio [OR] 1.19, [95% confidence intervals 1.10-1.28]) and Asian/Pacific Islanders (APIs) (OR 1.12 [1.03-1.23]) had an increased risk of deviations from treatment guidelines. Medicare/Medicaid increased the risk of deviations while treatment at high-volume facilities decreased its risk for all races/ethnicities. Deviations from guidelines were associated with an increased risk of death (hazard ratio 1.56 [1.50-1.63]. CONCLUSIONS: Racial disparities in the delivery of guideline-concordant therapy among GC patients are affected by several sociodemographic factors at the patient- and system-level.

Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution.

BACKGROUND: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. METHODS: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. RESULTS: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. CONCLUSIONS: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.

Inverse Association Between Gluteofemoral Obesity and Risk of Non-Cardia Gastric Intestinal Metaplasia.

BACKGROUND & AIMS: It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia. METHODS: We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric biopsy. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. RESULTS: Increasing body mass index (BMI) was not associated with risk of non-cardia gastric intestinal metaplasia (per unit BMI adjusted OR, 0.98; 95% CI, 0.96-1.00). Similarly, we found no associations with increase in waist circumference (per 10-cm increase adjusted OR, 0.94; 95% CI, 0.87-1.03) and waist-to-hip ratio (WHR) (per unit WHR adjusted OR, 2.34; 95% CI, 0.37-14.7). However, there was a significant inverse association with gastric intestinal metaplasia and increasing hip circumference, reflecting gluteofemoral obesity (per 10-cm increase adjusted OR, 0.89; 95% CI, 0.80-0.98). The inverse association was observed for both extensive and focal gastric intestinal metaplasia. CONCLUSIONS: The independent dimensions of adiposity (BMI, waist circumference) are not associated with increased risk of non-cardia gastric intestinal metaplasia. The inverse association between gluteofemoral obesity and risk of gastric intestinal metaplasia warrants additional study.

The Predictive Performance of Contemporary Guideline Recommendations for Helicobacter pylori Testing in a United States Population.

BACKGROUND: The Houston Consensus Conference and American College of Gastroenterology (ACG) have recommended Helicobacter pylori screening in United States populations with specific risk factors. However, the performance of these guidelines in clinical practice is not known. METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication in a safety-net hospital in Houston, TX during January 2015-December 2016. We tested the association between the presence of H pylori (histopathology, stool antigen, urea breath test, immunoglobulin G serology, or prior treatment) and H pylori risk factors using logistic regression models, reported as odds ratios and 95% confidence intervals (CIs). We evaluated the area under the receiver operating characteristic (AUROC) curve for predictive ability of individual risk factors identified by the Houston Consensus Conference and ACG. RESULTS: Of 942 patients, the prevalence of H pylori infection was 51.5%. The risk factors with the highest predictive performance included first-generation immigrant (AUROC, 0.59) and Hispanic or black race/ethnicity (AUROC, 0.57), whereas the remaining 7 risk factors/statements had low predictive value. A model that combined first-generation immigrant status, black or Hispanic race/ethnicity, dyspepsia, and reflux had higher predictive ability for H pylori infection (AUROC, 0.64; 95% CI, 0.61-0.68) than any individual risk factor. CONCLUSIONS: In this contemporary U.S. cohort, the performance of individual risk factors identified by the Houston Consensus Conference and ACG was generally low for predicting H pylori infection except for black or Hispanic race/ethnicity and first-generation immigrant status. A risk prediction model combining several risk factors had improved diagnostic performance and should be validated in future studies.

Controversies regarding management of Helicobacter pylori infections.

PURPOSE OF REVIEW: The recognition that Helicobacter pylori should be considered and treated as an infectious disease has yet to fundamentally change diagnostic and treatment practices and has resulted in many controversies. RECENT FINDINGS: We discuss the following controversies: whether the current 'per-patient' approach to H. pylori testing based on symptoms should be expanded to include achieving population-level H. pylori eradication, whether H. pylori should be approached as an infectious gastrointestinal disease similar to that of other infectious diseases of similar severity and outcome, whether treatment of H. pylori should be primarily empiric or based on antibiotic susceptibility and locally proven successful therapies as are other infectious diseases, whether it is necessary to obtain confirmation of treatment success in every patient treated for H. pylori , and whether potassium-competitive acid blockers should replace proton pump inhibitors in H. pylori therapy. SUMMARY: Available guidelines and meta-analyses do not yet address H. pylori as an infectious disease. The diagnosis and management and treatment success of H. pylori infections trails behind that of other important infectious diseases. We provide new insights and propose changes in the traditional understanding required to modernize the management of H. pylori infections.

Validation of a pre-endoscopy risk score for predicting the presence of gastric intestinal metaplasia in a U.S. population.

BACKGROUND AND AIMS: Surveillance of gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. Our purpose was to externally validate a predictive model for endoscopic GIM previously developed in a veteran population in a second U.S. METHODS: We previously developed a pre-endoscopy risk model for detection of GIM using 423 GIM cases and 1796 control subjects from the Houston Veterans Affairs Hospital. The model included sex, age, race/ethnicity, smoking, and Helicobacter pylori infection with an area under the receiver-operating characteristic curve (AUROC) of .73 for GIM and .82 for extensive GIM. We validated this model in a second cohort of patients from 6 Catholic Health Initiative (CHI)-St Luke's hospitals (Houston, Tex, USA) from January to December 2017. Cases were defined as having GIM on any gastric biopsy sample and extensive GIM as involving both the antrum and corpus. We further optimized the model by pooling both cohorts and assessing discrimination using AUROC. RESULTS: The risk model was validated in 215 GIM cases (55 with extensive GIM) and 2469 control subjects. Cases were older than control subjects (59.8 vs 54.7 years) with more nonwhites (59.1% vs 42.0%) and H pylori infections (23.7% vs 10.9%). The model applied to the CHI-St Luke's cohort had an AUROC of .62 (95% confidence interval [CI], .57-.66) for predicting GIM and of .71 (95% CI, .63-.79) for predicting extensive GIM. When the Veterans Affairs and CHI-St Luke's cohorts were pooled, discrimination of both models improved (GIM vs extensive GIM AUROC: .74 vs .82). CONCLUSIONS: A pre-endoscopy risk prediction model was validated and updated using a second U.S. cohort with robust discrimination for endoscopic GIM. This model should be evaluated in other U.S. populations to risk-stratify patients for endoscopic GIM screening.

Missed Opportunities for Screening or Surveillance Among Patients with Newly Diagnosed Non-cardia Gastric Adenocarcinoma.

BACKGROUND: Screening for gastric cancer is not recommended despite rising rates in certain U.S. POPULATIONS: We determined possible missed opportunities for the detection and surveillance of preneoplastic lesions among gastric cancer patients in a VA hospital. METHODS: This retrospective cohort study included consecutive, newly diagnosed non-cardia gastric adenocarcinoma patients from 11/2007 to 10/2018 at the Houston VA Hospital. We identified missed opportunities for screening based on risk factors (non-White race, smoking, alcohol, Helicobacter pylori infection, gastric ulcers, family history of gastric cancer). We additionally determined missed opportunities for surveillance of known high-risk lesions. Associations between receipt of prior endoscopy for screening or surveillance and cancer-related outcomes (stage, treatment, survival) were determined using logistic regression models. RESULTS: Among 91 gastric cancer patients, 95.6% were men, 51.6% were black, 12.1% were Hispanic, with mean age of 68.0 years (standard deviation 10.8 years). The most common risk factors included non-white race (68.1%), smoking (76.9%), alcohol use (59.3%) and prior H. pylori (12.1%). Most patients had ≥ 1 risk factor for gastric cancer (92.6%), and 76.9% had ≥ 2 risk factors. Only 25 patients (27.5%) had undergone endoscopy prior to cancer diagnosis. Of 14 with known high-risk lesions (i.e., gastric intestinal metaplasia, dysplasia, ulcer), only 2 (14.3%) underwent surveillance endoscopy. Receipt of prior endoscopy was not associated with differences in cancer outcomes. CONCLUSIONS: Most patients with newly diagnosed gastric cancer had ≥ 2 known risk factors for gastric cancer but never received prior screening endoscopy. Among the few with known prior preneoplastic lesions, endoscopic surveillance was not consistently performed.

Race/Ethnicity and Birthplace as Risk Factors for Gastric Intestinal Metaplasia in a Multiethnic United States Population.

INTRODUCTION: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk. METHODS: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed a risk prediction model of GIM risk. We additionally examined for associations using a composite variable combining race/ethnicity and birthplace. RESULTS: Among 267 cases with GIM and 1,842 controls, older age (vs <40 years: 40-60 years adjusted odds ratios (adjORs) 2.02; 95% CI 1.17-3.29; >60 years adjOR 4.58; 95% CI 2.61-8.03), Black race (vs non-Hispanic White: adjOR 2.17; 95% CI 1.31-3.62), Asian race (adjOR 2.83; 95% CI 1.27-6.29), and current smoking status (adjOR 2.04; 95% CI 1.39-3.00) were independently associated with increased GIM risk. Although non-US-born Hispanics had higher risk of GIM (vs non-Hispanic White: adjOR 2.10; 95% CI 1.28-3.45), we found no elevated risk for US-born Hispanics (adjOR 1.13; 95% CI 0.57-2.23). The risk prediction model had area under the receiver operating characteristic of 0.673 (95% CI 0.636-0.710) for discriminating GIM. DISCUSSION: We found that Hispanics born outside the United States were at increased risk of GIM, whereas Hispanics born in the United States were not, independent of Helicobacter pylori infection. Birthplace may be more informative than race/ethnicity when determining GIM risk among US populations.

Associations of Duration, Intensity, and Quantity of Smoking With Risk of Gastric Intestinal Metaplasia.

GOAL: Determine whether various dimensions of smoking increase risk for gastric intestinal metaplasia. BACKGROUND: Cigarette smoking has been implicated in the etiology of gastric cancer, but it is not clear if smoking is a risk factor for gastric intestinal metaplasia, a precursor lesion of gastric cancer. MATERIALS AND METHODS: We compared data from 385 gastric intestinal metaplasia cases and 1577 controls without gastric intestinal metaplasia recruited into a cross-sectional study at the Michael E. DeBakey VA Medical Center in Houston, Texas. All participants completed standardized questionnaires and underwent a study endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included participants with intestinal metaplasia on any noncardia gastric biopsy. We calculated odds ratios and associated 95% confidence intervals using multivariable logistic regression models. RESULTS: Compared with never smokers, current smokers had 2-fold increased risk for gastric intestinal metaplasia (odds ratio, 2.05; 95% confidence interval, 1.47-2.85). Among ever smokers, increasing duration and total dose were significantly associated with increased risk for gastric intestinal metaplasia (P-trend, 0.004 and 0.01, respectively). Among former smokers, risk for gastric intestinal metaplasia decreased over time and was no different to never smokers after 15 years smoking cessation. Cases with gastric intestinal metaplasia were more likely than controls to have Helicobacter pylori infection (53.2% vs. 21.7%); however, smoking effect on gastric intestinal metaplasia was not different by H. pylori infection status. CONCLUSIONS: Cigarette smoking is a risk factor for gastric intestinal metaplasia. Risk of gastric intestinal metaplasia among former smokers remained significantly elevated until 15 years postcessation.

Risk Score Using Demographic and Clinical Risk Factors Predicts Gastric Intestinal Metaplasia Risk in a U.S. Population.

BACKGROUND/AIMS: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S. METHODS: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. pylori infection alone and a baseline model including remaining terms without H. pylori. RESULTS: Male sex, older age, non-white race/ethnicity, smoking status, and H. pylori were associated with GIM risk. The expanded model including these terms had AUROC 0.73 (95%CI 0.71-0.76) for predicting GIM and AUROC 0.82 (95%CI 0.79-0.86) for extensive GIM. This model discriminated better than a model including only H. pylori (AUROC 0.66; 95%CI 0.63-0.68) and the baseline model (AUROC 0.67; 95%CI 0.64-0.70). The expanded model performed similarly among primary care (AUROC 0.75) and endoscopy (AUROC 0.73) patients. The expanded model showed sufficient internal validity (cross-validation AUROC 0.72) with little evidence of over-fitting. CONCLUSIONS: We develop and validate a non-invasive risk model for GIM detection in a U.S. population that included terms for sex, age, race/ethnicity, smoking status, and H. pylori infection. Validated risk models would identify individuals with GIM who should be referred for endoscopic screening.

Ethnicity Is an Important Consideration in Screening for Gastric Intestinal Metaplasia.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precursor to gastric adenocarcinoma, making it an attractive target for early detection by endoscopy. The aim of this study was to determine the prevalence, risk factors, and associated histologic findings of GIM among patients undergoing endoscopy in a diverse US population. METHODS: We conducted a retrospective, cross-sectional study of patients undergoing elective endoscopy with gastric biopsies at 6 academic and community centers in Houston, Texas. GIM prevalence was estimated with a 95% confidence interval (CI), and patient demographic and clinical characteristics were summarized using mean with standard deviation, or frequency with percentage. Generalized estimating equations (GEE) were used to compare characteristics between those with and without GIM. RESULTS: Our final cohort consisted of 2685 patients, including 216 cases with GIM and 2469 controls. The prevalence of GIM in our cohort was 8.04% (95% CI 7.07%, 9.14%). The mean age of GIM cases was higher than in the control group (59.8 vs 54.7 years, p < 0.0001). The prevalence of GIM in Asians, Hispanic, Black and Non-Hispanic Whites (NHW) was 14.7%, 11.7%, 9.8% and 5.8%, respectively. On multivariable analysis, factors associated with GIM include age (adj. OR 1.32 per 10 year increase, p < 0.0001), habitual smoking (adj. OR 1.68, p < 0.0001), and race (compared to NHW: Asian, adj. OR 2.34, p = 0.010; Hispanic, adj. OR 2.15, p < 0.001; Black, adj. OR 1.61, p < 0.001). CONCLUSION: Asians, Hispanics, and African Americans have higher rates of GIM than NHW. Ethnicity should be an important consideration on determining who to screen for GIM in the US.

Prevalence of Gastric Intestinal Metaplasia in a Multiethnic US Veterans Population.

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, from February 2008 to August 2013. All participants completed a study questionnaire on sociodemographic and clinical characteristics and underwent upper endoscopy with gastric mapping (7 biopsy sites). Cases were classified as having gastric intestinal metaplasia if intestinal metaplasia was detected in 1 or more noncardia gastric biopsies; noncases were participants without evidence of gastric intestinal metaplasia. We used logistic regression models to estimate odds ratios (ORs) and 95% CI values to examine the association between race or ethnicity and gastric intestinal metaplasia and performed a mediation analysis to determine whether H pylori and gastritis affected observed associations. RESULTS: We included 415 cases with gastric intestinal metaplasia and 1764 noncases. The prevalence of gastric intestinal metaplasia was highest among Hispanic patients (29.5%; 95% CI, 23.7%-36.1%), followed by African American (25.5%; 95% CI, 22.4%-28.9%) and non-Hispanic white patients (13.7%; 95% CI, 11.9%-15.7%). After we adjusted for age, sex, and smoking, African American (OR, 1.87; 95% CI, 1.44-2.44) and Hispanic race or ethnicity (OR, 2.32; 95% CI, 1.61-3.34) and H pylori infection (OR, 3.65; 95% CI, 2.79-4.55) were associated with an increased risk of gastric intestinal metaplasia. H pylori infection alone accounted for 33.6% of the association of race or ethnicity with gastric intestinal metaplasia, and 55.5% of the association when combined with acute and chronic gastritis. CONCLUSIONS: Hispanic and African American patients have an increased risk for gastric intestinal metaplasia, determined by upper endoscopy biopsy analysis, compared with non-Hispanic white patients. This increase in risk was partially independent of H pylori infection.

Automated software-assisted diagnosis of esophageal squamous cell neoplasia using high-resolution microendoscopy.

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm. METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) and confidence level (high or low) without and with knowledge of the software overlay highlighting abnormal nuclei and software interpretation. The criterion standard was histopathology consensus diagnosis by 2 pathologists. RESULTS: The endoscopists had a higher mean sensitivity (84.3%, standard deviation [SD] 8.0% vs 76.3%, P = .004), lower specificity (75.0%, SD 5.2% vs 85.3%, P < .001) but no significant difference in accuracy (81.1%, SD 5.2% vs 79.4%, P = .26) of ESCN detection compared with the automated software algorithm. With knowledge of the software algorithm, the specificity of the endoscopists increased significantly (75.0% to 80.1%, P = .002) but not the sensitivity (84.3% to 84.8%, P = .75) or accuracy (81.1% to 83.1%, P = .13). The increase in specificity was among novices (P = .008) but not experts (P = .11). CONCLUSIONS: The software algorithm had lower sensitivity but higher specificity for ESCN detection than endoscopists. Using computer-assisted diagnosis, the endoscopists maintained high sensitivity while increasing their specificity and accuracy compared with their initial diagnosis. Automated HRME interpretation would facilitate widespread usage in resource-poor areas where this portable, low-cost technology is needed.

Dietary Factors and Gastric Intestinal Metaplasia Risk Among US Veterans.

BACKGROUND: Studies on diet and gastric intestinal metaplasia (GIM) risk are lacking in US populations. AIM: To determine the associations of dietary factors and risk of GIM among a US population with typical American diet. METHODS: We analyzed data from a cross-sectional study of veterans attending primary care and endoscopy clinics at the Houston VA Medical Center. Patients completed a 110-item Block Food Frequency Questionnaire then underwent upper endoscopy with gastric mapping biopsies. We compared cases defined by GIM on ≥ 1 non-cardia gastric biopsy to controls without GIM. Associations of dietary factors and GIM were estimated using logistic regression models as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Among 423 GIM cases and 1796 controls, cases were older (62.1 vs. 59.9 years) and more likely to be male (97.2% vs. 90.8%) and non-White (58.6% vs. 39.0%). GIM cases had lower fat intake (percent kcal from fat tertile 1: 43.6% vs. 33.4%) and higher carbohydrate intake (percent kcal from carbohydrate T3: 41.8% vs. 33.3%) than controls. Adjusting for age, gender, race, smoking, and Helicobacter pylori, percent kcal from carbohydrates (T3 vs. T1: OR 1.35, 95% CI 1.08-1.67), fruit intake (T3 vs. T1: OR 1.28, 95% CI 1.02-1.61), and fiber intake (T3 vs. T1: OR 1.37, 95% CI 1.04-1.80) were associated with GIM. In subgroup analyses, these associations were primarily seen in non-White patients. CONCLUSIONS: Few dietary factors, including high carbohydrate intake, are associated with increased risk of GIM in US populations, independent of H. pylori or smoking.

Demographic and Lifestyle Risk Factors for Gastric Intestinal Metaplasia Among US Veterans.

OBJECTIVES: The risk of noncardia gastric cancer is increased in the presence of gastric intestinal metaplasia. We aimed to identify demographic and lifestyle factors independently associated with the risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of patients attending primary care and endoscopy clinics at the Michael E. DeBakey VA Medical Center in Houston, Texas, between February 2008 and August 2013. All patients completed standardized questionnaires and underwent endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included patients with intestinal metaplasia on any noncardia gastric biopsy; we defined extensive gastric intestinal metaplasia as antrum and corpus involvement. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression models. RESULTS: We identified 423 cases with gastric intestinal metaplasia and 1,796 controls without gastric intestinal metaplasia. Older age (vs <60 years: 60-69 years AdjOR, 1.50; 95% CI, 1.17-1.93; ≥70 years AdjOR, 2.12; 95% CI, 1.48-3.04), male sex (AdjOR, 2.76; 95% CI, 1.50-5.10), nonwhite race/ethnicity (vs non-Hispanic white: Hispanic, AdjOR, 2.66; 95% CI, 1.89-3.76; black, AdjOR, 2.36; 95% CI, 1.85-3.02), and current smoking status (AdjOR, 1.78; 95% CI, 1.29-2.48) were independently associated with gastric intestinal metaplasia. These risk factors remained statistically significantly associated with gastric intestinal metaplasia after adjusting for Helicobacter pylori infection, and their effect sizes were larger for associations with extensive gastric intestinal metaplasia compared with focal gastric intestinal metaplasia. DISCUSSION: Older age, male sex, nonwhite race/ethnicity, and current smoking status were the nonendoscopic factors independently associated with gastric intestinal metaplasia in a predominantly nonimmigrant US population.

No Barrett's-No Cancer: A Proposed New Paradigm for Prevention of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma is inflammation-associated cancer with a recognizable preneoplastic stage, Barrett's. Barrett's describes the metaplastic transformation of esophageal squamous mucosa into columnar epithelium that typically results secondary to mucosal damage caused by acidic gastroduodenal reflux. Continued acid reflux may then result in mucosal inflammation which results in progressive inflammation-induced genetic instability that may eventuate in esophageal adenocarcinoma. Barrett's is the only recognized precursor lesion to esophageal carcinoma. Barrett's mucosa is unique among preneoplastic lesions; ablation therapy results in restitution of a squamous epithelium reducing or eliminating accumulated genetic instabilities and resetting the biological clock progressing toward invasive cancer. However, recurrence of Barrett's after ablation is common. We propose that both Barrett's and recurrence of Barrett's after ablation can be prevented and discuss how current approaches to therapy for gastroesophageal reflux disease, for Barrett's screening, chemoprevention, and ablation therapy all might be reconsidered. We propose (1) improved approaches to Barrett's prevention, (2) universal Barrett's screening by linking Barrett's screening to colon cancer screening, (3) ablation of all Barrett's mucosa along with (4) acid-suppressive-antireflux therapy tailored to prevent development of Barrett's or the recurrence of Barrett's after ablation therapy. We propose that ultimately, treatment decisions for gastroesophageal reflux disease and prevention of Barrett's and esophageal carcinoma should be based on assessing and maintaining esophageal mucosal integrity. This will require development and verification of specific measurements that reliably correlate with prevention of Barrett's. We outline the new research and technical advances needed to cost-effectively achieve these goals.

Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients.

BACKGROUND: Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers. AIMS: We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients. METHODS: We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up. RESULTS: PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84-1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87-1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89-1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29-1.74) and HCC (HR 1.31; 95% CI 1.23-1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use. CONCLUSION: Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients.

Prevalence of Helicobacter pylori Positive Non-cardia Gastric Adenocarcinoma Is Low and Decreasing in a US Population.

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear. METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models. RESULTS: Of 91 patients with gastric adenocarcinoma, most were men (N = 87, 95.6%), black (N = 47, 51.6%), with mean age at diagnosis of 68.0 years (SD 10.8). In addition to gastric cancer biopsy histopathology, 74 patients (81.3%) had ≥ 1 testing for H. pylori, including antibody serology (n = 34), non-cancer gastric biopsy histopathology (n = 63), or stool antigen (n = 1). The overall prevalence of H. pylori infection was 38.5% and 45.9% among patients with ≥ 2 H. pylori tests. The proportions of H. pylori positive gastric cancer decreased from 50.0% (2007-2010) to 43.4% (2011-2014) and 29.3% (2015-2018) (p = 0.096). Active/acute gastritis (adjOR 3.74), atrophic gastritis (adjOR 15.30), and gastric intestinal metaplasia (adjOR 3.65) were associated with H. pylori positive gastric cancer. DISCUSSION: The prevalence of H. pylori infection among patients with non-cardia gastric adenocarcinoma is relatively low (38.5-45.9%) and decreasing over time. This finding suggests there may be other important causal factors apart from H. pylori for gastric adenocarcinoma.